KR20060009933A - 시아노플루오로피롤리딘 유도체 - Google Patents
시아노플루오로피롤리딘 유도체 Download PDFInfo
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- KR20060009933A KR20060009933A KR1020057021698A KR20057021698A KR20060009933A KR 20060009933 A KR20060009933 A KR 20060009933A KR 1020057021698 A KR1020057021698 A KR 1020057021698A KR 20057021698 A KR20057021698 A KR 20057021698A KR 20060009933 A KR20060009933 A KR 20060009933A
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- South Korea
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- substituted
- substituent
- substituents selected
- carbon atoms
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- SSKBPPNEPSALEP-UHFFFAOYSA-N 1-fluoropyrrolidine-2-carbonitrile Chemical class FN1CCCC1C#N SSKBPPNEPSALEP-UHFFFAOYSA-N 0.000 title description 6
- 150000001875 compounds Chemical class 0.000 claims abstract description 208
- -1 cyanofluoropyrrolidine compound Chemical class 0.000 claims abstract description 173
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 61
- 150000003839 salts Chemical class 0.000 claims abstract description 38
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 27
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 22
- 239000003814 drug Substances 0.000 claims abstract description 14
- 201000010099 disease Diseases 0.000 claims abstract description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 9
- 229910052731 fluorine Chemical group 0.000 claims abstract description 7
- 208000026278 immune system disease Diseases 0.000 claims abstract description 7
- 206010012601 diabetes mellitus Diseases 0.000 claims abstract description 6
- 125000001424 substituent group Chemical group 0.000 claims description 435
- 125000004432 carbon atom Chemical group C* 0.000 claims description 252
- 125000000217 alkyl group Chemical group 0.000 claims description 92
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 66
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 55
- 125000005843 halogen group Chemical group 0.000 claims description 45
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 44
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 claims description 42
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 claims description 42
- 238000000034 method Methods 0.000 claims description 40
- 125000003277 amino group Chemical group 0.000 claims description 39
- 125000003118 aryl group Chemical group 0.000 claims description 37
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 36
- 125000001072 heteroaryl group Chemical group 0.000 claims description 33
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 32
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 24
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 24
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 22
- 125000000623 heterocyclic group Chemical group 0.000 claims description 20
- 125000000392 cycloalkenyl group Chemical group 0.000 claims description 18
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 18
- 125000003342 alkenyl group Chemical group 0.000 claims description 17
- 125000005842 heteroatom Chemical group 0.000 claims description 17
- 125000004429 atom Chemical group 0.000 claims description 16
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 16
- 125000003545 alkoxy group Chemical group 0.000 claims description 15
- 229910052757 nitrogen Inorganic materials 0.000 claims description 13
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 13
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 12
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 12
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
- 125000000000 cycloalkoxy group Chemical group 0.000 claims description 11
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 10
- 229910052760 oxygen Inorganic materials 0.000 claims description 10
- 229910052717 sulfur Inorganic materials 0.000 claims description 10
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
- 239000001301 oxygen Substances 0.000 claims description 9
- 239000011593 sulfur Substances 0.000 claims description 9
- 230000001668 ameliorated effect Effects 0.000 claims description 7
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 7
- 125000001544 thienyl group Chemical group 0.000 claims description 7
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 claims description 6
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 6
- 125000001153 fluoro group Chemical group F* 0.000 claims description 6
- 125000002950 monocyclic group Chemical group 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- 150000004677 hydrates Chemical class 0.000 claims description 5
- 125000004043 oxo group Chemical group O=* 0.000 claims description 4
- 125000005017 substituted alkenyl group Chemical group 0.000 claims description 4
- 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims description 2
- 239000004480 active ingredient Substances 0.000 claims description 2
- 125000006165 cyclic alkyl group Chemical group 0.000 claims description 2
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical group FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 abstract description 2
- 239000011737 fluorine Chemical group 0.000 abstract description 2
- 101100134922 Gallus gallus COR5 gene Proteins 0.000 abstract 1
- 102000035195 Peptidases Human genes 0.000 abstract 1
- 108091005804 Peptidases Proteins 0.000 abstract 1
- 229910052739 hydrogen Inorganic materials 0.000 abstract 1
- 239000001257 hydrogen Substances 0.000 abstract 1
- 230000003449 preventive effect Effects 0.000 abstract 1
- 235000019833 protease Nutrition 0.000 abstract 1
- 229940124597 therapeutic agent Drugs 0.000 abstract 1
- 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 134
- 238000003786 synthesis reaction Methods 0.000 description 100
- 230000015572 biosynthetic process Effects 0.000 description 98
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 88
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 84
- 238000006243 chemical reaction Methods 0.000 description 81
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 60
- 239000000243 solution Substances 0.000 description 59
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 58
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- LNWWQYYLZVZXKS-UHFFFAOYSA-N 1-pyrrolidin-1-ylethanone Chemical compound CC(=O)N1CCCC1 LNWWQYYLZVZXKS-UHFFFAOYSA-N 0.000 description 49
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 48
- 239000002904 solvent Substances 0.000 description 48
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 32
- QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical compound CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 32
- 239000000126 substance Substances 0.000 description 32
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- 230000002829 reductive effect Effects 0.000 description 30
- 238000001816 cooling Methods 0.000 description 28
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 28
- PTSPKMINRZNMJA-UHFFFAOYSA-N 1-acetyl-4-fluoropyrrolidine-2-carbonitrile Chemical compound CC(=O)N1CC(F)CC1C#N PTSPKMINRZNMJA-UHFFFAOYSA-N 0.000 description 27
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
- IETPCANGMKPUAP-UHFFFAOYSA-N 1-acetyl-4-fluoropyrrolidine-2-carbonitrile dihydrochloride Chemical compound Cl.Cl.C(C)(=O)N1C(CC(C1)F)C#N IETPCANGMKPUAP-UHFFFAOYSA-N 0.000 description 23
- 238000003756 stirring Methods 0.000 description 20
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 20
- 239000000203 mixture Substances 0.000 description 19
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 18
- 238000010898 silica gel chromatography Methods 0.000 description 18
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 17
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 17
- MDNLPMUOELGCNE-UHFFFAOYSA-N 1-(3-fluoropyrrolidin-1-yl)ethanone Chemical compound CC(=O)N1CCC(F)C1 MDNLPMUOELGCNE-UHFFFAOYSA-N 0.000 description 16
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 16
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 16
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 14
- 235000011114 ammonium hydroxide Nutrition 0.000 description 14
- 239000002274 desiccant Substances 0.000 description 14
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 14
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 12
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 11
- 230000000694 effects Effects 0.000 description 11
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 10
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical group C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 10
- 229960004132 diethyl ether Drugs 0.000 description 10
- 239000000843 powder Substances 0.000 description 10
- 125000000547 substituted alkyl group Chemical group 0.000 description 10
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 9
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 230000005764 inhibitory process Effects 0.000 description 9
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 9
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 8
- 235000017557 sodium bicarbonate Nutrition 0.000 description 8
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
- 239000000725 suspension Substances 0.000 description 8
- 150000007529 inorganic bases Chemical class 0.000 description 7
- 238000004519 manufacturing process Methods 0.000 description 7
- 229910000027 potassium carbonate Inorganic materials 0.000 description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 230000002459 sustained effect Effects 0.000 description 7
- OPCJOXGBLDJWRM-UHFFFAOYSA-N 1,2-diamino-2-methylpropane Chemical compound CC(C)(N)CN OPCJOXGBLDJWRM-UHFFFAOYSA-N 0.000 description 6
- 125000002941 2-furyl group Chemical group O1C([*])=C([H])C([H])=C1[H] 0.000 description 6
- 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 6
- 239000007864 aqueous solution Substances 0.000 description 6
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 6
- 239000000872 buffer Substances 0.000 description 6
- GLNDAGDHSLMOKX-UHFFFAOYSA-N coumarin 120 Chemical compound C1=C(N)C=CC2=C1OC(=O)C=C2C GLNDAGDHSLMOKX-UHFFFAOYSA-N 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- ZUFQCVZBBNZMKD-UHFFFAOYSA-M potassium 2-ethylhexanoate Chemical compound [K+].CCCCC(CC)C([O-])=O ZUFQCVZBBNZMKD-UHFFFAOYSA-M 0.000 description 6
- VYPDUQYOLCLEGS-UHFFFAOYSA-M sodium;2-ethylhexanoate Chemical compound [Na+].CCCCC(CC)C([O-])=O VYPDUQYOLCLEGS-UHFFFAOYSA-M 0.000 description 6
- 241000700159 Rattus Species 0.000 description 5
- PASDCCFISLVPSO-UHFFFAOYSA-N benzoyl chloride Chemical compound ClC(=O)C1=CC=CC=C1 PASDCCFISLVPSO-UHFFFAOYSA-N 0.000 description 5
- 239000003795 chemical substances by application Substances 0.000 description 5
- 229910052801 chlorine Inorganic materials 0.000 description 5
- 125000001309 chloro group Chemical group Cl* 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 125000002541 furyl group Chemical group 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 230000004060 metabolic process Effects 0.000 description 5
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 description 5
- 125000006505 p-cyanobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C#N)C([H])([H])* 0.000 description 5
- 125000006239 protecting group Chemical group 0.000 description 5
- CDDGNGVFPQRJJM-UHFFFAOYSA-N 3-fluoropyrrolidine Chemical compound FC1CCNC1 CDDGNGVFPQRJJM-UHFFFAOYSA-N 0.000 description 4
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 4
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 238000007112 amidation reaction Methods 0.000 description 4
- 125000004244 benzofuran-2-yl group Chemical group [H]C1=C(*)OC2=C([H])C([H])=C([H])C([H])=C12 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 125000004122 cyclic group Chemical group 0.000 description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 4
- JARKCYVAAOWBJS-UHFFFAOYSA-N hexanal Chemical compound CCCCCC=O JARKCYVAAOWBJS-UHFFFAOYSA-N 0.000 description 4
- ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
- DVSDBMFJEQPWNO-UHFFFAOYSA-N methyllithium Chemical compound C[Li] DVSDBMFJEQPWNO-UHFFFAOYSA-N 0.000 description 4
- 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 4
- 239000002994 raw material Substances 0.000 description 4
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 4
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 4
- FPQQSJJWHUJYPU-UHFFFAOYSA-N 3-(dimethylamino)propyliminomethylidene-ethylazanium;chloride Chemical compound Cl.CCN=C=NCCCN(C)C FPQQSJJWHUJYPU-UHFFFAOYSA-N 0.000 description 3
- KEPSJISIUDGGSI-UHFFFAOYSA-N 3h-benzimidazole-5-carbonyl chloride Chemical compound ClC(=O)C1=CC=C2N=CNC2=C1 KEPSJISIUDGGSI-UHFFFAOYSA-N 0.000 description 3
- 206010004446 Benign prostatic hyperplasia Diseases 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- MEQYZLVMLXTKEV-UHFFFAOYSA-N CC(=O)NC1C(CN2CCC(Cl)C12)OC(=O)NCC1C2CN3CCC(O2)C13 Chemical compound CC(=O)NC1C(CN2CCC(Cl)C12)OC(=O)NCC1C2CN3CCC(O2)C13 MEQYZLVMLXTKEV-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- 241000725303 Human immunodeficiency virus Species 0.000 description 3
- 102000004877 Insulin Human genes 0.000 description 3
- 108090001061 Insulin Proteins 0.000 description 3
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- 208000004403 Prostatic Hyperplasia Diseases 0.000 description 3
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- 230000002152 alkylating effect Effects 0.000 description 3
- 125000005530 alkylenedioxy group Chemical group 0.000 description 3
- 125000005529 alkyleneoxy group Chemical group 0.000 description 3
- 150000001408 amides Chemical class 0.000 description 3
- 239000008346 aqueous phase Substances 0.000 description 3
- 210000004369 blood Anatomy 0.000 description 3
- 239000008280 blood Substances 0.000 description 3
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000012230 colorless oil Substances 0.000 description 3
- MGNCLNQXLYJVJD-UHFFFAOYSA-N cyanuric chloride Chemical compound ClC1=NC(Cl)=NC(Cl)=N1 MGNCLNQXLYJVJD-UHFFFAOYSA-N 0.000 description 3
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 238000010511 deprotection reaction Methods 0.000 description 3
- 230000002708 enhancing effect Effects 0.000 description 3
- 238000006911 enzymatic reaction Methods 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 3
- 229940125396 insulin Drugs 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000012074 organic phase Substances 0.000 description 3
- 239000012071 phase Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 108090000765 processed proteins & peptides Proteins 0.000 description 3
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- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D207/16—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P13/08—Drugs for disorders of the urinary system of the prostate
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/04—Anorexiants; Antiobesity agents
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P5/48—Drugs for disorders of the endocrine system of the pancreatic hormones
- A61P5/50—Drugs for disorders of the endocrine system of the pancreatic hormones for increasing or potentiating the activity of insulin
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Diabetes (AREA)
- Rheumatology (AREA)
- Obesity (AREA)
- Hematology (AREA)
- Endocrinology (AREA)
- Immunology (AREA)
- Emergency Medicine (AREA)
- Pain & Pain Management (AREA)
- Child & Adolescent Psychology (AREA)
- Dermatology (AREA)
- Urology & Nephrology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Physical Education & Sports Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyrrole Compounds (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2003137062 | 2003-05-15 | ||
| JPJP-P-2003-00137062 | 2003-05-15 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20060009933A true KR20060009933A (ko) | 2006-02-01 |
Family
ID=33447245
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020057021698A KR20060009933A (ko) | 2003-05-15 | 2004-05-17 | 시아노플루오로피롤리딘 유도체 |
Country Status (11)
| Country | Link |
|---|---|
| US (1) | US20060293297A1 (es) |
| EP (1) | EP1627870A1 (es) |
| JP (1) | JPWO2004101514A1 (es) |
| KR (1) | KR20060009933A (es) |
| CN (1) | CN1791575A (es) |
| AU (1) | AU2004238719A1 (es) |
| CA (1) | CA2525442A1 (es) |
| MX (1) | MXPA05012274A (es) |
| NO (1) | NO20055971L (es) |
| RU (1) | RU2005139134A (es) |
| WO (1) | WO2004101514A1 (es) |
Families Citing this family (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| MX2007004305A (es) | 2004-10-12 | 2007-06-18 | Glenmark Pharmaceuticals Sa | Inhibidores novedosos de dipeptidil peptidasa iv, composiciones farmaceuticas que los contienen y procedimientos para su preparacion. |
| DOP2006000008A (es) | 2005-01-10 | 2006-08-31 | Arena Pharm Inc | Terapia combinada para el tratamiento de la diabetes y afecciones relacionadas y para el tratamiento de afecciones que mejoran mediante un incremento de la concentración sanguínea de glp-1 |
| ZA200802857B (en) | 2005-09-14 | 2009-09-30 | Takeda Pharmaceutical | Dipeptidyl peptidase inhibitors for treating diabetes |
| KR101368988B1 (ko) | 2005-09-16 | 2014-02-28 | 다케다 야쿠힌 고교 가부시키가이샤 | 디펩티딜 펩티다제 억제제 |
| WO2007112347A1 (en) | 2006-03-28 | 2007-10-04 | Takeda Pharmaceutical Company Limited | Dipeptidyl peptidase inhibitors |
| PE20071221A1 (es) | 2006-04-11 | 2007-12-14 | Arena Pharm Inc | Agonistas del receptor gpr119 en metodos para aumentar la masa osea y para tratar la osteoporosis y otras afecciones caracterizadas por masa osea baja, y la terapia combinada relacionada a estos agonistas |
| PL1971862T3 (pl) | 2006-04-11 | 2011-04-29 | Arena Pharm Inc | Sposoby stosowania receptora GPR119 w celu identyfikacji związków przydatnych w zwiększeniu masy kostnej osobnika |
| TW200838536A (en) | 2006-11-29 | 2008-10-01 | Takeda Pharmaceutical | Polymorphs of succinate salt of 2-[6-(3-amino-piperidin-1-yl)-3-methyl-2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-ylmethy]-4-fluor-benzonitrile and methods of use therefor |
| US8551524B2 (en) | 2008-03-14 | 2013-10-08 | Iycus, Llc | Anti-diabetic combinations |
| EP2146210A1 (en) | 2008-04-07 | 2010-01-20 | Arena Pharmaceuticals, Inc. | Methods of using A G protein-coupled receptor to identify peptide YY (PYY) secretagogues and compounds useful in the treatment of conditions modulated by PYY |
| CN103804266B (zh) * | 2014-02-21 | 2016-06-08 | 张家港威胜生物医药有限公司 | 一种维达列汀中间体的合成方法 |
| EA201791982A1 (ru) | 2015-03-09 | 2020-02-17 | Интекрин Терапьютикс, Инк. | Способы лечения неалкогольной жировой болезни печени и/или липодистрофии |
| EP3606527A1 (en) | 2017-04-03 | 2020-02-12 | Coherus Biosciences, Inc. | Ppar-gamma agonist for treatment of progressive supranuclear palsy |
| CN108164528B (zh) * | 2018-03-31 | 2019-03-22 | 杭州巴洛特生物科技有限公司 | 一种酰胺类衍生物及其在高血压、高血脂和动脉粥样硬化中的应用 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| TW492957B (en) * | 1996-11-07 | 2002-07-01 | Novartis Ag | N-substituted 2-cyanopyrrolidnes |
| TWI243162B (en) * | 2000-11-10 | 2005-11-11 | Taisho Pharmaceutical Co Ltd | Cyanopyrrolidine derivatives |
| JPWO2003095425A1 (ja) * | 2002-05-09 | 2005-09-15 | 大正製薬株式会社 | シアノピロリジン誘導体 |
| JP2004026820A (ja) * | 2002-05-09 | 2004-01-29 | Taisho Pharmaceut Co Ltd | ジペプチジルペプチダーゼｉｖ阻害剤 |
-
2004
- 2004-05-17 WO PCT/JP2004/006983 patent/WO2004101514A1/ja not_active Application Discontinuation
- 2004-05-17 CN CNA200480013353XA patent/CN1791575A/zh active Pending
- 2004-05-17 EP EP04733467A patent/EP1627870A1/en not_active Withdrawn
- 2004-05-17 AU AU2004238719A patent/AU2004238719A1/en not_active Abandoned
- 2004-05-17 CA CA002525442A patent/CA2525442A1/en not_active Abandoned
- 2004-05-17 US US10/556,896 patent/US20060293297A1/en not_active Abandoned
- 2004-05-17 JP JP2005506281A patent/JPWO2004101514A1/ja not_active Withdrawn
- 2004-05-17 KR KR1020057021698A patent/KR20060009933A/ko not_active Application Discontinuation
- 2004-05-17 RU RU2005139134/04A patent/RU2005139134A/ru not_active Application Discontinuation
- 2004-05-17 MX MXPA05012274A patent/MXPA05012274A/es not_active Application Discontinuation
-
2005
- 2005-12-15 NO NO20055971A patent/NO20055971L/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| NO20055971L (no) | 2005-12-15 |
| CA2525442A1 (en) | 2004-11-25 |
| MXPA05012274A (es) | 2006-02-10 |
| US20060293297A1 (en) | 2006-12-28 |
| JPWO2004101514A1 (ja) | 2006-07-13 |
| EP1627870A1 (en) | 2006-02-22 |
| AU2004238719A1 (en) | 2004-11-25 |
| CN1791575A (zh) | 2006-06-21 |
| RU2005139134A (ru) | 2006-08-27 |
| WO2004101514A1 (ja) | 2004-11-25 |
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| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |